RELATIONSHIP BETWEEN PLASMA PERHEXILINE CONCENTRATION AND SYMPTOMATICSTATUS DURING SHORT-TERM PERHEXILINE THERAPY

We tested the hypothesis that resolution versus persistence of symptom atic ischaemia and/or development of nausea/dizziness on the third day of loading with perhexiline maleate (PM), is correlated with perhexil ine plasma concentrations after the standard loading phase in patients with acute coronary syndromes. Forty consecutive patients with either unstable angina pectoris or non-Q-wave myocardial infarction with per sistent angina pectoris, despite maximal pharmacological therapy (othe r than PM), were studied. All patients received PM 400 mg/day for 3 da ys and 200 mg/day thereafter. On days 2 and 3 observers blinded to the 72-96 h plasma perhexiline concentration assessed the patient regardi ng episodes of angina and/or nausea/dizziness. On the third day of loa ding with PM, 12 patients experienced angina and 11 patients had nause a and/or dizziness. Plasma perhexiline concentrations at 72-96 h varie d widely: mean 0.46 +/- 0.26 (range 0.11-1.77) mu g/ml. There was a re lationship of borderline statistical significance between resolution o f anginal symptoms and plasma perhexiline concentration >0.15 mu g/ml (p = 0.055), There was a close relationship between emergence of nause a/dizziness with plasma perhexiline concentration >0.60 mu g/ml (p < 0 .01). We conclude that this study (a) suggests that PM exerts incremen tal antianginal effects over those of other antiischaemic agents in pa tients with acute coronary syndromes and (b) establishes that the deve lopment of nausea and/or dizziness in such patients is strongly predic tive of accumulation of perhexiline beyond the therapeutic range of th e drug.